Random Dermatology MCQ - Cockayne syndrome

A 3-year-old boy presents with photosensitivity, short stature, and prematurely aged facial features. Physical examination reveals dry, scaly skin and progressive sensorineural hearing loss. His parents report he has had severe sunburns with minimal sun exposure. Which of the following is the most likely underlying molecular defect?

A) Defective nucleotide excision repair (ERCC6 gene)
B) Mutation in KRT5 or KRT14
C) Deficiency of complement C1 esterase inhibitor
D) Abnormal copper transport (ATP7A gene)
E) Mutation in PTCH1

Correct Answer: A) Defective nucleotide excision repair (ERCC6 gene)

Explanation

This patient has Cockayne syndrome, a DNA repair disorder caused by mutations in ERCC6 (or ERCC8), leading to:

1. Photosensitivity: Inability to repair UV-induced DNA damage.

2. Progeroid features: Premature aging due to defective transcription-coupled repair.

3. Neurologic degeneration: Sensorineural deafness, cognitive decline.

Why Not Other Options?

• (B) KRT5/KRT14 mutations cause epidermolysis bullosa simplex (blistering).

• (C) C1 inhibitor deficiency causes hereditary angioedema (not photosensitivity).

• (D) ATP7A defects cause Menkes disease (kinky hair, hypotonia).

• (E) PTCH1 mutations cause Gorlin syndrome (BCCs, odontogenic keratocysts).

Diagnostic Clues:

• "Cachectic dwarfism" with deep-set eyes and thin nose.

• MRI: Calcifications in basal ganglia.

Management:

• Strict photoprotection (UV avoidance).

• Symptomatic care (hearing aids, physical therapy).